This is a study of the biochemistry of heart valves, a vascular connective tissue. The collagen, GAS and glycoprotein of the ground substance will be studied in detail. Besides these, we are planning to study the mechanism of valvular lesions and vegetation formation in endocarditis and arteriosclerosis in experimental animals. Cyanogen bromide cleavage techniques will be utilized to characterize chain type of collagen in bovine and human heart valves. This will be extended to diseased valves (mitral stenotic) and to those removed from patients for "insufficiency". Solubilization and characterization of valvular collagen will be attempted using trypsin or pepsin at 4 degrees C and also some other extractants. Metabolic studies will be performed "in vitro" to study biosynthesis and degradation of collagen using radioactive 14C-proline and 14C-lysine. When 14C-lysine is used, its conversion into hydroxylysine and the extent of glycosylation of hydroxylysine will be determined. Proline and lysine oxidase activities will also be measured. Studies of gycosaminoglycans and glycoproteins will include "in vitro" biosynthesis using proper radioactive precursors (3H-glucosamine, 3H-fucose, 14C-acetate and 14C-threonine) and also isolation and characterization of these macromolecules in the heart valves. Quantitative analyses of collagen, GAG and glycoproteins will be done on diseased human valves obtained by balbectomy and regular autopsy. The pathological valves will include cases of mitral stenosis and insufficiency. Animal models (chicken and rabbits) will be utilized to study the mechanism of various valvular lessions. This will include both "in vivo" and "in vitro" experiments involving radioactive precursors used for metabolic studies of collagen, GAG and glycoproteins.